Identification of Rare LRP5 Variants in a Cohort of Males with Impaired Bone Mass

Osteoporosis is the most common bone disease characterized by reduced bone mass and increased bone fragility. Genetic contribution is one of the main causes of primary osteoporosis; therefore, both genders are affected by this skeletal disorder. Nonetheless, osteoporosis in men has received little attention, thus being underestimated and undertreated. The aim of this study was to identify novel genetic variants in a cohort of 128 males with idiopathic low bone mass using a next-generation sequencing (NGS) panel including genes whose mutations could result in reduced bone mineral density (BMD). Genetic analysis detected in eleven patients ten rare heterozygous variants within the LRP5 gene, which were categorized as VUS (variant of uncertain significance), likely pathogenic and benign variants according to American College of Medical Genetics and Genomics (ACMG) guidelines. Protein structural and Bayesian analysis performed on identified LRP5 variants pointed out p.R1036Q and p.R1135C as pathogenic, therefore suggesting the likely association of these two variants with the low bone mass phenotype. In conclusion, this study expands our understanding on the importance of a functional LRP5 protein in bone formation and highlights the necessity to sequence this gene in subjects with idiopathic low BMD.

T-Cell Mediated Inflammation in Postmenopausal Osteoporosis

Osteoporosis is the most prevalent metabolic bone disease that affects half the women in the sixth and seventh decade of life. Osteoporosis is characterized by uncoupled bone resorption that leads to low bone mass, compromised microarchitecture and structural deterioration that increases the likelihood of fracture with minimal trauma, known as fragility fractures. Several factors contribute to osteoporosis in men and women. In women, menopause – the cessation of ovarian function, is one of the leading causes of primary osteoporosis. Over the past three decades there has been growing appreciation that the adaptive immune system plays a fundamental role in the development of postmenopausal osteoporosis, both in humans and in mouse models. In this review, we highlight recent data on the interactions between T cells and the skeletal system in the context of postmenopausal osteoporosis. Finally, we review recent studies on the interventions to ameliorate osteoporosis.

Osteoporosis in Men: A Review of an Underestimated Bone Condition

Osteoporosis is called the ‘silent disease’ because, although it does not give significant symptoms when it is not complicated, can cause fragility fractures, with serious consequences and death. Furthermore, the consequences of osteoporosis have been calculated to weigh heavily on the costs of health systems in all the countries. Osteoporosis is considered a female disease. Actually, the hormonal changes that occur after menopause certainly determine a significant increase in osteoporosis and the risk of fractures in women. However, while there is no doubt that women are more exposed to osteoporosis and fragility fractures, the literature clearly indicates that physicians tend to underestimate the osteoporosis in men. The review of the literature done by the authors shows that osteoporosis and fragility fractures have a high incidence also in men; and, furthermore, the risk of fatal complications in hip fractured men is higher than that for women. The authors report the evidence of the literature on male osteoporosis, dwelling on epidemiology, causes of osteoporosis in men, diagnosis, and treatment. The analysis of the literature shows that male osteoporosis is underscreened, underdiagnosed, and undertreated, both in primary and secondary prevention of fragility fractures.

Egyptian consensus on treat-to-target approach for osteoporosis: a clinical practice guideline from the Egyptian Academy of bone health and metabolic bone diseases

Background This study was carried out to achieve an Egyptian expert consensus on a treat-to-target management strategy for osteoporosis using Delphi technique. A scientific committee identified researchers and clinicians with expertise in osteoporosis in Egypt. Delphi process was implemented (2 rounds) to establish a consensus on 15 clinical standards: (1) concept, (2) diagnosis, (3) case identification, (4) whom to treat, (5) who should treat?, (6) case stratification and intervention thresholds, (7) falls risk, (8) investigations, (9) treatment target, (10) management, (11) optimum treatment duration, (12) monitoring, (13) drug holiday, (14) osteoporosis in men, and (15) post-fracture care and fracture liaison service. Results The surveys were sent to an expert panel (n = 25), of whom 24 participated in the two rounds. Respondents were drawn from different governorates and health centres across Egypt including the Ministry of Health. Most of the participants were rheumatologists (76%), followed by internists (8%), orthopaedic doctors (4%), rehabilitation doctors (4%), primary care (4%), and ortho-geriatrics (4%) physicians. Seventy-two recommendations, categorised into 15 sections, were obtained. Agreement with the recommendations (rank 7–9) ranged from 83.4 to 100%. Consensus was reached (i.e. ≥ 75% of respondents strongly agreed or agreed) on the wording of all 15 clinical standards identified by the scientific committee. An algorithm for the management of postmenopausal osteoporosis has been suggested. Conclusion A wide and representative panel of experts established a consensus regarding the management of osteoporosis in Egypt. The developed guidelines provide a comprehensive approach to the assessment and management of osteoporosis for all Egyptian healthcare professionals who are involved in its management.